In a 2016 draft guidance to industry, FDA encouraged incorporating histologic evaluation in ulcerative colitis (UC) clinical trials to reliably conclude “mucosal healing” or histological remission as a treatment goal. However, there is no community consensus on how to define mucosal healing and, even with a standard definition, the field would lack standardized protocols for measuring this treatment target endpoint. Standardized assessment of histologic disease activity in UC clinical trials is challenging for many reasons, including variability in how studies collect mucosal biopsies (e.g., the optimum number and location), lack of fully validated histology scoring systems, and absence of standard definitions of histologic improvement and remission. The lack of standardized measurement of mucosal healing constitutes a major challenge for UC drug development and negatively impacts treatment options for patients with this serious, chronic, inflammatory bowel disease. This project aims to address this gap by establishing a common methodology for a histologic measurement of mucosal healing in treatment of UC. This measurement must demonstrate clear prognostic value for predicting long-term patient outcomes. The final results of this project will help generate a common protocol and white paper that drives industry consensus and will be submitted to FDA in order to influence regulatory guidance for companies conducting UC clinical trials in the future.
This proposal will build a unique dataset to define the best practice for measuring mucosal healing by leveraging existing datasets from at least 3 organizations to:
- Establish the optimum number and locations of biopsies required to determine histological inflammation in UC.
- Standardize the histopathologic measurement of mucosal healing that correlates with better clinical response and long-term patient outcomes.
- Validate an objective machine learning methodology for scoring of mucosal healing that can be used in clinical trials, regulatory approvals, and clinical practice.
- U.S. Food and Drug Administration
- AbbVie, Inc*
- Boehringer Ingelheim International GmbH*
- Bristol Myers Squibb Company *
- Crohn’s & Colitis Foundation*
- Eli Lilly and Company*
- Janssen Research & Development, LLC*
- Kenneth Rainin Foundation*
- Pfizer, Inc*
- Regeneron Pharmaceuticals*
- Takeda Pharmaceutical Company Limited (Takeda) *
- Icahn School of Medicine – Mount Sinai Health System
- University of Oxford
- Western University & London Health Science Centre
*Provided financial or in-kind support for this program.